Alkyl-borons

In 6.5.2.1 it is shown that BF3 and BCI3 add to phosphine Pt complexes without cleaving the B—X bond. In contrast, aryl and alkyl boron halides are added oxidatively with phosphine Pt complexes - ... 

The mechanism involves the dissociation of the coordinated borane 15 to generate a monoborane intermediate 16. Coordination of the alkene would generate the alkene borane complex. A /3-borylalkylhydride with B-H stabilization is certainly an important resonance structure of 17. An intramolecular reaction would extrude the alkyl boronate ester product and coordination of HBcat would regenerate the monoborane intermediate. 

Recently, this methodology has been extended to the couphng of alkyl, allyhc, 1-alkenyl and 1-alkynyl halides with 1-alkenyl and even alkyl boron reagents. 

Several nonreductive methods for cleavage of benzyl groups have also been developed. Treatment with s-butyllithium, followed by reaction with trimethyl borate and then hydrogen peroxide, liberates the alcohol.24 The lithiated ether forms an alkyl boronate, which is oxidized as discussed in Section 4.9.2. 

These gels are based on immobilised alkyl boronic acids. They have a selective affinity for 1,2- or 1,3-diol groupings such as those found in catechol-containing molecules such as dopamine and in sugars or glycosides. 

The use of a-halo(alkyl) boronic esters in asymmetric synthesis provides state of the art stereoselection1-3. The diastereomeric ratio of the a-halo boronic esters synthesized as intermediates is routinely in the 100 1 range. However, with the proper choice of chiral director, displacement of the oc-halogen provides a second stcrcodifferentiation step, after which diastereomeric ratios may exceed 1000 1 4. 

Reaction of an (S, S )-diol (a/ )-0 -chloro boronic ester 4 with a Grignard or lithium reagent leads to an intermediate borale complex30 5 which rearranges to a secondary alkyl boronic ester 6. One use of the secondary alkyl boronic ester 6 is oxidation with alkaline hydrogen peroxide, which is known to proceed with retention of configuration31, to form the corresponding chiral secondary alcohol. 

Results obtained in the conversion of boronic esters of C2 symmetry 1 or 2 to a-chloro boronic esters 4 and on to secondary alkyl boronic esters 6 are summarized in Table 1. For example, the data with R2 = isopropyl, utilized material of only 97% ce38 and significantly underestimated the diastereoselectivity. 

Tablet. Diastereoselection in the Synthesis of Secondary Alkyl Boronic Esters. 

In the initial discovery of the asymmetric synthesis of a-chloro boronic esters 3, the diastereomeric ratios of 3 were estimated by reaction with Grignard reagents to form secondary alkyl boronic esters 5 and deboronation with hydrogen peroxide to secondary alcohols of known absolute configuration and rotation40. 

S)-Pinanediol l,2-Bis(benzyloxy)alkyl]boronate General Procedure ... 

As noted for the Heck reaction, aryl, alkenyl, and alkynyl bromides, iodides, and triflates are best for the oxidative addition. However, aromatic, heteroaromatic, alkenyl, and even alkyl boronic acids and esters can be coupled effectively. The reaction appears almost oblivious to other functional groups present ... 

The alkyl-boron bond is readily cleaved by hydrogen peroxide (these reactions are normally carried out in presence of alkali) according to... 

The influence of the metal atom on mechanism is particularly well illustrated by the pronounced tendency of the alkyls of boron and aluminium to react via coordination complexes in which the metal atom is four-co-ordinate. It is no coincidence that the prime examples of substitution by mechanism SE2(co-ord) occur in reactions of alkyl-boron compounds. 

Jadhav, P. K. Man, H.-W. Direct synthesis of [a-[(tert-butoxycarbonyl)amino]alkyl]boronates from (a-haloalkyl)boronates./. Org. Chem. 1996, 61,7951-7954. 

Asymmetric hydroboration of prochiral alkenes has been achieved using transition metal catalysts and chiral phosphines as ligands to obtain enantiomerically pure alkyl boronates <1997CC173>. Catalysts such as Rh(COD)2+BF4 , Rh(COD)2+Cl, Rh+BF4 , etc., in combination with chiral phosphines like DIOP 71, BINAP 72, CHIRAPHOS 73, DIPAMP 74, BDPP 75, ferrocene-based diphosphines 76<1999TL4977>, etc., have been employed for the asymmetric hydroboration of prochiral alkenes with moderate to high ee (DIOP = 2,3-0-isopropylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino)butane BINAP = 2,2-bis(diphenyl-phos-phanyl)-l,1-binaphthyl CHIRAPHOS = 2,3-bis(diphenylphosphino)butane DIPAMP = l,2-bis[(2-methoxyphe-nyl)phenylphosphino]ethane BDPP = 2,4-bis(diphenylphosphino)pentane). 

The dichloro compound is even less stable. It was obtained as an impure material from the reaction with BCI3. Attempts to alkylate boron-bonded chlorine with RLi or RMgX were unsuccessful, as were attempts to alkylate the (B)-NR2 groups with aluminium alkyls. 

The GC separation of dihydric alcohols of natural origin may be carried out after their conversion into alkyl boronates. Methaneboronates of ceramides [44] were prepared by treatment with methaneboronic acid in pyridine solution. They offer excellent GC properties on stationary phases of the OV-1 and SE-30 types and are particularly suitable for GC-MS. 

One practical disadvantage of these systems lies in the fact that relatively high concentrations of Lewis acids are needed to aehieve alternation. Thus methyl methaerylate and styrene alternate perfeetly with azodiisobutyronitrile initiation at 50°C when the molar ratio of ZnCL to methyl methacrylate is 0.4. Alternation is less exact, however, when this ratio is 0.25. Alkyl boron halides like ethyl boron diehloride are effective at lower concentrations and act also as initiators if oxygen is present. 

W. L. Jorgensen 1994 Ascorbic cid Ventura 1995 Alkanes Kaminski 1994 Alkyl boronic acids... 

Masamune has documented the addition of optically active ester enolates that afford lanfi-aldol adducts in superb yields and impressive stereoselectivity (Eq. (8.3)) [4]. The generation of a boryl enolate from 8 follows from groundbreaking studies of ester enolization by Masamune employing dialkyl boryl tri-flates and amines [5]. Careful selection of di-n-alkyl boron triflate (di-n-butyl versus dicyclopentyl or dicyclohexyl) and base (triethyl amine versus Hiinigs base) leads to the formation of enolates that participate in the <2u//-selective propionate aldol additions. Under optimal conditions, 8 is treated with 1-2 equiv of di-c-hex-yl boron triflate and triethyl amine at -78 °C followed by addition of aldehyde the products 9 and 10 are isolated in up to 99 1 antv.syn diastereomeric ratio. The asymmetric aldol process can be successfully carried out with a broad range of substrates including aliphatic, aromatic, unsaturated, and functionalized aldehydes. 

Aryl and alkyl boron compounds have received significant research attention as building blocks in organic synthesis. One of the most straightforward methods for making such compounds is the reaction of a boronic acid ester with a Grignard reagent. However, the reaction... 

If all three groups on borane can migrate, as in normal trialkyl borane, tertiary alcohols are the products. Three migrations from boron to carbon go via the unstable ketone 236 and epoxide 238 to the relatively stable /-alkyl boron derivative 239 that is oxidised to the /-alcohol 240. A /-alkyl group must migrate here as there is no alternative. 

Using a Suzuki disconnection, we intend to add an alkyl boronic acid 260 to an -vinyl bromide 259 (from but-l-yne) and the boronic acid will come from hydroboration of a simple alkene 261 rather than an alkyne. 

You will have realised that the Suzuki coupling is the best of those we have mentioned. It is regiospecific as the positions for coupling are marked, one with a boronic acid and one with a halide. It does not use toxic tin. It can be used for all the aryl, heteroaryl, vinyl, benzyl and other groups that Heck and Stille use and in addition it can be used for saturated alkyl boronic acids with P-hydrogen atoms without P-elimination. It is not surprising that it is very widely used and we give a few representative examples. 

The most distinctive contribution of the Suzuki to modern methodology is the coupling of alkyl boronic acids, formed by hydroboration of alkenes, to vinyl and aryl halides.47 The simple mono-substituted alkene 279 reacts with 9-BBN followed by Suzuki coupling with aryl iodides to give products 281 in good yield regardless of the nature or the position of the substituents.48... 

The palladium-catalysed reactions with alkenyl, aryl, and heteroaryl halides or triflates as one partner ( electrophilic ) and alkenes (Heck), aryl or vinyl stannanes (Stille) or aryl, vinyl and even alkyl boronic acids (Suzuki) as the other ( nucleophilic ) partner provide a synthetic method of astonishing power and versatility. These reactions are only just starting to be explored and great things are expected of them. 

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